Michael addition of amines and thiols to dehydroalanines proceeds better in frozen water

14 May 2004

Workers at BMS were studying the Michael addition of amines and thiols to a dehydroalanine side chain of some nocathiacins. When the reaction was carried out at ambient temperature in water the yield was 50% after 24 hours. At 5° C the yield was 70% after 24 hours, but a 90% yield could be achieved if the reaction mixture was frozen at -2°C for 5-6 hours. This is not just a temperature effect as carrying out the reaction at -20°C under conditions whereby the reaction remained liquid, using aqueous methanol as solvent, gave the product in 70% yield after 120 hours.

Tetrahedron Letters, 2004 , 45(5) , 1059-1063.